Serotonin, corpus callosum, and autism

The most consistent anatomical characteristic of ASD is a reduction in the size of the corpus callosum - a sign of underconnectivity between the two cortical hemispheres. The neurotransmitter serotonin (5HT) plays a critical role during early brain development, and 5HT synthesis is altered in autistic individuals at early ages. The most challenging and clinically relevant aspects of this proposal is the attempt to link the recent drastic increase of ASD to the increased number of mothers taking antidepressant drugs, namely selective serotonin reuptake inhibitors (SSRIs), during pregnancy and nursing. The central hypothesis in this study is that abnormal regulation of 5HT during early brain development interferes with myelin formation and the establishment of normal inter-hemispheric connections. The proposed experiments are designed to address this hypothesis by studying anatomical, neurochemical, physiological, and behavioral effects following increased serotonin activation in rats just prior to and after birth. Rat mothers and rat pups will be treated with the common anti-depressant citalopram (the most selective SSRI). Results from this study may help develop a future animal model for ASD and could hold the key to linking serotonin dysfunction during early brain development to increased rates of maternal SSRI usage during pregnancy and nursing.